Figure 2.

Inhibitor and activator of PKM2 role in the inflammation and cancer development. A. In acute inflammation, shikonin, the inhibitor of PKM2, can reduce the expression of dimeric PKM2, thereby inhibiting glycolysis, reducing the release of inflammasomes, and inhibiting excessive inflammation. In cancer tissues, shikonin can directly affects the Warburg effect and suppress cancer growth by reducing the expression of dimeric PKM2. It also can downregulate dimeric PKM2 to produce lactic acid of aerobic glycolysis, and restraint the polarization of TAM1 to TAM2, so indirectly suppress cancer growth. B. In the inflammatory response induced by LPS, the dimeric PKM2 can promote the transformation of macrophages to M1 type and evoke the occurrence of inflammation. TEPP-48/DASA-48, the activator of PKM2, can convert dimeric PKM2 into tetrameric PKM2, which reduces glycolysis, and then decrease the production of inflammatory markers such as IL-1β, lastly inhibits inflammation. In cancer cells, the PKM2 activator directly reduces the Warburg effect of cancer cells and inhibits caner growth. Otherwise, it can also indirectly suppress cancer growth by reducing the production of lactic acid, which restraint the polarization of TAM2.